Smoking during pregnancy has been shown to decrease infant birth weight and to substantially increase both perinatal morbidity and mortality. Among the major components of cigarette smoke, the physiologic aberrations produced by carbon monoxide have been extensively investigated. Less is known about the physiologic effects of nicotine on the pregnant uterus and its contents. Utilizing a well-established sheep model, specifically designed for continuous blood flow measurements and blood sampling, we have been able to delineate the effects of nicotine on uterine blood flow. Following systemic nicotine infusion, uterine blood flow decreases, a response which is mediated by release of catecholamines. We propose to extend these observations by simultaneous measurements of: (1) umbilical blood flow, (2) maternal and fetal plasma nicotine concentrations, (3) fetal acid base status, and (4) fetal plasma catecholamine concentrations. The proposed study should provide information relating to the mechanisms by which nicotine influences uterine and umbilical blood flow, and ultimately improve our understanding of how smoking endangers fetal health.